Amdipharm


Regency House
Miles Gray Road
Basildon
Essex
SS14 3AF


Telephone: +44 (0)870 777 7675
Facsimile: +44 (0)870 777 7875
Medical Information direct line: +44 (0)1268 823 049
Medical Information e-mail: medinfo@amdipharm.com
Medical Information facsimile: +44 (0)1268 535 287
Document last updated on the eMC: Wed 29 September 2004
Diconal Tablets
Table of Contents

1. NAME OF THE MEDICINAL PRODUCT

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

3. PHARMACEUTICAL FORM

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

4.2 Posology and method of administration

4.3 Contraindications

4.4 Special warnings and precautions for use

4.5 Interaction with other medicinal products and other forms of interaction

4.6 Pregnancy and lactation

4.7 Effects on ability to drive and use machines

4.8 Undesirable effects

4.9 Overdose

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

5.2 Pharmacokinetic properties

5.3 Preclinical safety data

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

6.2 Incompatibilities

6.3 Shelf life

6.4 Special precautions for storage

6.5 Nature and contents of container

6.6 Special precautions for disposal and other handling

7. MARKETING AUTHORISATION HOLDER

8. MARKETING AUTHORISATION NUMBER(S)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10. DATE OF REVISION OF THE TEXT



1. NAME OF THE MEDICINAL PRODUCT To the top of the page

Diconal Tablets.


2. QUALITATIVE AND QUANTITATIVE COMPOSITION To the top of the page

Each tablet contains 10 mg of Dipipanone Hydrochloride BP and 30 mg of Cyclizine Hydrochloride BP, coloured deep pink, scored and coded 'F3A'.


3. PHARMACEUTICAL FORM To the top of the page

Tablet.


4. CLINICAL PARTICULARS To the top of the page


4.1 Therapeutic indications To the top of the page

Diconal Tablets are indicated for the management of moderate to severe pain in medical and surgical conditions in which morphine may be indicated.

Cyclizine is effective in preventing nausea and vomiting associated with the administration of narcotic analgesics.



4.2 Posology and method of administration To the top of the page

Adults: The initial dose in all conditions is one tablet every 6 hours. It is unwise to exceed this dose in view of the difficulty in accurately predicting the initial central effects of dipipanone.

Should this dose fail to prove adequate analgesia, as in severe intractable pain or when other potent opioids have been used, it may be increased by half a tablet every six hours.

It is seldom necessary to exceed a dose of 30 mg dipipanone given 6-hourly (i.e. 12 tablets in 24 hours).

Children: There is no specific information on the use of Diconal in children. Diconal is very rarely indicated in children and dosage guidelines cannot be stated.

Use in the elderly: There is no specific information on the use of Diconal in elderly patients. In common with opioid drugs, Diconal may be expected to cause confusion in this age group, and careful monitoring is advised (see Precautions).



4.3 Contraindications To the top of the page

Diconal is contra-indicated in individuals who are hypersensitive to dipipanone or cyclizine.

Diconal is generally contra-indicated in patients with respiratory depression, especially in the presence of cyanosis and excessive bronchial secretions.

Diconal should not be given during an attack of bronchial asthma.

Diconal is generally contra-indicated in the presence of acute alcoholism, head injury and raised intracranial pressure.

Diconal is contra-indicated in individuals receiving monoamine oxidase inhibitors, or within 14 days of stopping such treatment.

Diconal is contra-indicated in patients with ulcerative colitis since in common with other narcotic analgesics it may precipitate toxic dilatation or spasm of the colon.

As with all narcotic analgesics Diconal should not be administered to patients with severe hepatic impairment as it may precipitate hepatic encephalopathy.

In severe renal impairment Diconal, in common with all narcotic analgesics, may precipitate coma and should not be administered.

Diconal, in common with morphine and most other narcotics, may cause spasm of the biliary and renal tracts; it is contra-indicated in these conditions.



4.4 Special warnings and precautions for use To the top of the page

The repeated use of Diconal may lead to tolerance and physical dependence as well as to psychological dependence on the product.

Misuse of Diconal has been reported, particularly by young addicts who have previously been dependent on, or have misused other agents both opiate and non-opiate. Extreme caution is warranted when prescribing Diconal to this group of patients.

Diconal should be used with extreme caution in the presence of the following: hypothyroidism; adrenocortical insufficiency; prostatic hypertrophy; hypotension secondary to hypovolaemic shock; diabetes mellitus.

Diconal is metabolised in the liver and excreted along with its metabolites in the urine. Where not contra-indicated in patients with impaired hepatic and/or renal function, Diconal should be given at less than the usual recommended dose, and the patient's response used as a guide to further dosage requirements.

Extreme caution should be exercised when administering Diconal to patients with phaeochromocytoma, since hypertension has been reported in association with other potent opioids.

No data are available as to whether or not dipipanone has carcinogenic, mutagenic or teratogenic potential. It is not known whether cyclizine has carcinogenic or mutagenic potential. Some animal studies are interpreted as indicating that cyclizine may be teratogenic, but relevance to the human situation is not known.

In a study involving prolonged administration of cyclizine to male and female rats, there was no evidence of impaired fertility after continuous treatment for 90-100 days. There are no similar data for dipipanone. There is no information on the effect of Diconal on human fertility.



4.5 Interaction with other medicinal products and other forms of interaction To the top of the page

The central nervous system depressant effects of Diconal may be increased by phenothiazine drugs, alcohol, sedatives and tricyclic antidepressants. Concurrent administration of some phenothiazines increases the respiratory depressant effects of narcotic analgesics and also produces hypotension.

Because of its anticholinergic activity, cyclizine may enhance the side effects of other anticholinergic agents.

Analgesic effects of opioid drugs tend to be enhanced by co-administration of dexamphetamine, however their use in combination is not recommended.



4.6 Pregnancy and lactation To the top of the page

The use of Diconal during pregnancy is not recommended. No data are available on the therapeutic use of Diconal in human pregnancy. It may be anticipated that if given in the last trimester, Diconal would cause withdrawal symptoms in the neonate.

Diconal is not recommended for use in labour because of its potential to cause respiratory depression in the neonate.

No data are available on the excretion of dipipanone, cyclizine or their metabolites in human milk.



4.7 Effects on ability to drive and use machines To the top of the page

Ambulatory patients receiving Diconal should be cautioned against driving cars or operating machinery in view of its tendency to cause drowsiness.



4.8 Undesirable effects To the top of the page

The adverse effects of dipipanone are common to all opioid agents, and may include:- respiratory depression; mental clouding, drowsiness and sedation, confusion, mood changes, euphoria, dysphoria, psychosis, restlessness, miosis and raised intracranial pressure; constipation, nausea and vomiting; sweating, facial flushing and hypotension; urticaria and rashes; difficulty with micturition; biliary and renal tract spasm; vertigo.

In addition, cyclizine may cause urticaria, drug rash, drowsiness, dryness of the mouth, nose and throat, blurred vision, tachycardia, urinary retention, constipation, restlessness, nervousness, insomnia and auditory and visual hallucinations, particularly when dosage recommendations have been exceeded. Other central nervous system effects which have been reported rarely include dystonia, dyskenesia, extrapyramidal motor disturbances, tremor, twitching, muscle spasms, convulsions, disorientation, dizziness, decreased consciousness and transient speech disorders. Cholestatic jaundice has occurred in association with cyclizine. Single case reports have been documented of fixed drug eruption; generalised chorea; hypersensitivity hepatitis and agranulocytosis.



4.9 Overdose To the top of the page

The signs of overdosage with Diconal are typically those of opioid poisoning i.e. respiratory depression, pin-point pupils, hypotension, circulatory failure and deepening coma. Mydriasis may replace miosis as asphyxia intervenes. Drowsiness, floppiness, miosis and apnoea have been reported in children, as have convulsions.

General supportive measures should be employed as required. Gastric lavage should be performed if indicated. The specific opioid antagonist naloxone is the treatment of choice for the reversal of coma and the restoration of spontaneous respiration; the literature should be consulted for details of appropriate dosage. Patients should be monitored closely for at least 48 hours after recovery in case of relapse, since the duration of action of the antagonist may be substantially shorter than that of dipipanone.


5. PHARMACOLOGICAL PROPERTIES To the top of the page


5.1 Pharmacodynamic properties To the top of the page

The onset of analgesic action of dipipanone is approximately one hour and lasts for 4 to 6 hours. Cyclizine produces its anti-emetic effect within 2 hours and lasts for approximately 4 hours.



5.2 Pharmacokinetic properties To the top of the page

Dipipanone is absorbed from the gastro-intestinal tract. It is metabolised in the liver and excreted in the urine and faeces, although data on the proportions of parent compound and metabolites so excreted are lacking.

In healthy adult volunteers, the administration of a single oral dose of 50 mg cyclizine resulted in a peak plasma concentration of approximately 70 nanogram/ml occurring approximately 2 hours after drug administration. The plasma elimination half-life was approximately 20 hours.

The N-demethylated derivative, norcyclizine, has been identified as a metabolite of cyclizine. Norcyclizine has little antihistaminic (H1) activity compared with cyclizine and has a plasma elimination half life of approximately 20 hours. After a single oral dose of 50 mg cyclizine given to a single adult male volunteer, urine collected over the following 24 hours contained less than 1% of the total dose administered.



5.3 Preclinical safety data To the top of the page

No additional data of relevance.


6. PHARMACEUTICAL PARTICULARS To the top of the page


6.1 List of excipients To the top of the page

Lactose, starches, dye (FD and C Red No. 3), gelatin, magnesium stearate.



6.2 Incompatibilities To the top of the page

None stated.



6.3 Shelf life To the top of the page

60 months.



6.4 Special precautions for storage To the top of the page

Store below 25°C. Protect from light. Keep dry.



6.5 Nature and contents of container To the top of the page

PVC/aluminium foil blister packs containing 50 tablets.



6.6 Special precautions for disposal and other handling To the top of the page

None stated.


7. MARKETING AUTHORISATION HOLDER To the top of the page

Amdipharm PLC

Trading as Amdipharm

Regency House

Miles Gray Road

Basildon

Essex

SS14 3AF


8. MARKETING AUTHORISATION NUMBER(S) To the top of the page

PL 20072/0009


9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION To the top of the page

15th September 2003


10. DATE OF REVISION OF THE TEXT To the top of the page

SUPPORTING INFORMATION To the top of the page
Patient Information Leaflet:
Diconal Tablets